Brain Oxygen Extraction by Using MRI in Older Individuals: Relationship to Apolipoprotein E Genotype and Amyloid Burden.
Journal
Radiology
ISSN: 1527-1315
Titre abrégé: Radiology
Pays: United States
ID NLM: 0401260
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
pubmed:
24
4
2019
medline:
7
3
2020
entrez:
24
4
2019
Statut:
ppublish
Résumé
Background Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset Alzheimer disease. However, the mechanisms by which APOE4 affects the brain, underpinning this risk, have not been fully elucidated. Purpose To investigate the influence of APOE4 on global cerebral oxygen extraction fraction (OEF) and possible mediation through amyloid burden by using MRI-based brain oxygen extraction technique. Materials and Methods Participants were enrolled from a longitudinal prospective study, the Biomarkers for Older Controls at Risk for Dementia study (data collected from January 2015 to December 2017), of whom 35% (50 of 143 participants) were APOE4 carriers. OEF was measured by using a T2-relaxation-under-spin-tagging MRI technique with a 3.0-T MRI system. PET acquired with carbon 11-labeled Pittsburgh compound B tracer was available in 119 participants to measure amyloid burden. Cognitive performance was assessed by using domain-specific composite scores including executive function, episodic memory, visual-spatial processing, and language. Linear regression analysis was performed to investigate the relationship between APOE4, OEF, and amyloid burden. The association between OEF and cognitive function was studied for the entire study cohort and separately for the APOE4 carriers and noncarriers. Results A total of 143 cognitively healthy individuals (mean age 6 standard deviation, 69.1 years 6 8.2; 57 men and 86 women) were studied. APOE4 genetic status was associated with lower OEF (noncarriers, 41.1% 6 5.8; one E4 allele, 40.1% 6 4.9; two E4 alleles, 36.7% 6 4.5; P = .03). Furthermore, among APOE4 carriers, lower OEF correlated with lower executive function scores (b = 0.079 z score for each percent change in OEF; P = .03). Amyloid burden and OEF were independently associated with APOE4 but were not associated with one another, suggesting that the effect of APOE4 on OEF is not mediated by amyloid. Conclusion MRI-based brain oxygen extraction shows that cognitively healthy carriers of the apolipoprotein E4 gene manifest diminished brain oxygen extraction capacity independent of amyloid burden. ©RSNA, 2019
Identifiants
pubmed: 31012816
doi: 10.1148/radiol.2019182726
pmc: PMC6604795
mid: NIHMS1037953
doi:
Substances chimiques
Amyloid beta-Peptides
0
Apolipoprotein E4
0
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
140-148Subventions
Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG055153
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG033655
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AG999999
Pays : United States
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